Study procedures
An institutional clinical database was utilized to capture study data and included evaluations for transfusional hemosiderosis with initial MRI and contemporaneous measurements of serum iron, total iron binding concentration (TIBC), transferrin saturation, and ferritin. Subsequent MRI evaluations, initiation and/or adjustments in therapy with chelation or phlebotomy were also collected. Data regarding the patients’ cancer type, date of diagnosis, requirement of hematopoietic stem cell transplant (HSCT), as well as adverse outcomes including relapse and/or death were also collected. Subjects were categorized by cancer therapy using the validated Intensity of Treatment Rating Scale (ITR-3).13
Measures of siderosis using MRI were collected using gradient echo and spin echo pulse sequences on 1.5 Tesla magnets. The relaxation rates R2 and R2* were estimated using custom Matlab routines, where R2 and R2* are the reciprocals of T2 and T2*, respectively. Liver R2* was converted to liver iron concentration (LIC) using the calibration by Wood et al.14 Severity of LIC, pancreatic R2*, and cardiac T2* were determined by predefined clinically important thresholds.15-17 LIC by MRI18 was defined as mild (LIC 3 to <7 mg/g), moderate (7 to <15 mg/g), and severe (15 mg/g or greater). Pancreatic R2* from 27 to <100 Hz was considered mild to moderate and 100 Hz or greater indicated severe pancreatic siderosis based on association of R2* > 100 with cardiac siderosis and abnormal glucose metabolism.19 Cardiac T2* 20-30 ms was defined as borderline, while T2*< 20 ms indicated cardiac siderosis. Severity of pituitary siderosis was determined by predefined thresholds of R2 values converted to Z-scores, where Z ≥ 2 was considered clinically significant. Pituitary volume in the anterior and posterior planes was also converted to Z-scores, where Z ≤ -2 was consistent with volume loss.20,21 These pituitary parameters have been related to the risk of clinical hypogonadism in thalassemia patients.22